The managers' perspectives on service providing in women's harm reduction centers during the COVID-19 pandemic: mixed method study.

BACKGROUND: The COVID-19 pandemic posed significant challenges for managers overseeing women's harm reduction centers. This study seeks to capture managers' perspectives on the service providing in women's harm reduction centers during the COVID-19 pandemic. METHODS: This convergent mixed-method study conducted in three provinces of Iran: Tehran, Khuzestan, and Kermanshah. The study was carried out between January and May 2023. In the quantitative part, the researchers utilized reports from 10 center managers. A researcher-designed questionnaire was employed to collect data on a wide range of services and referrals provided by the centers. The qualitative part of the research involved conventional content analysis and included 12 individual interviews. Two directors from the Ministry of Health and ten managers of women's harm reduction centers participated in the interviews. During the interpretation phase, the researchers compared the quantitative and qualitative findings to obtain a comprehensive understanding of the topic. RESULTS: During the quantitative stage of the study, it was observed that all the managers were women, with an average age of 40.7 ± 7 years. More than half of the managers had obtained a postgraduate education (n = 6, 60%), and a majority of them were married (n = 7, 70%). Additionally, 40% of the managers (n = 4) were working as contractors. During the non-COVID-19 period, there were higher coverage by centers and residents, more referrals of non-injecting drug users and sex workers, and a higher number of group counseling sessions in all three provinces compared to the COVID-19 period. The qualitative analysis revealed two primary themes: "challenges" and "capabilities." CONCLUSIONS: During the COVID-19 pandemic, providing some services and client referrals decreased in the centers, and center managers faced increased challenges. Many of these challenges were in the communication, executive, management, structure, education, financial, civilization, facilities, and socio-cultural sectors. Managers used their skills to manage and control these challenges. It is important to focus on these challenges and managerial capabilities to effectively handle future crises.

Knowledge, attitude, and practice of Iranian adults toward Persian Medicine: a national survey.

BACKGROUND: Previous researches conducted in both developed and developing countries have demonstrated a rising trend in the utilization of complementary and alternative medicine. The World Health Organization has underscored the importance of studying the prevalence and determinants of such alternative practices. This study delves into the knowledge, attitudes, and practices of Iranian adults towards Persian medicine, a distinct form of complementary and alternative medicine, through a national survey for the first time. METHODS: A total of 2882 Iranian adults (aged ≥ 15 years) were randomly chosen from all regions. Data were gathered through structured door-to-door interviews using a survey questionnaire, wherein cases were selected randomly based on postal codes, and interviewers completed the forms at the participants' residences. RESULTS: Approximately 46% of the subjects exhibited familiarity with Persian Medicine. The study revealed that the primary sources of knowledge about Persian Medicine were family, relatives, and friends, with only 2.9% indicating medical staff as their source of information. Furthermore, the study indicated that 21% of participants expressed a strong interest in using Persian Medicine, while 30.3% did not. When comparing Persian medicine to modern medicine, respondents indicated that Persian medicine is more cost-effective and has fewer side effects, yet modern medicine is more widely used globally; although, the majority responded "I don't know" to other questions. The results also demonstrated that approximately 37% of the participants had a history of Persian Medicine utilization in their lifetime. CONCLUSION: This study revealed that Iranian adults have low reliable knowledge (from medical staff, Persian medicine books and other publications) and limited familiarity with Persian medicine, with about one third of the participants expressing disinterest (attitude) and over half of them having not utilized this form of medicine (practice).

Urtica pilulifera L. seed extract promotes folliculogenesis and alleviates the diminished ovarian reserve in the Balb/c mice model: An experimental study.

Background: Urtica pilulifera L. seed (UPS) is a Persian traditional medicine prescription that positively affects female infertility. Objective: This study aimed to evaluate the beneficial effects of UPS on a diminished ovarian reserve (DOR) model induced by cyclophosphamide in Balb/c mice. Materials and Methods: A single intraperitoneal (75 mg/kg) of cyclophosphamide was administered to establish a DOR model. 25 female Balb/c mice (6-8 wk, 25 ± 2 gr) were randomly divided into 5 groups (n = 5/each), including control (normal saline), model (DOR), DOR+50, DOR+100, and DOR+200 (mg/kg UPS, gavage) groups for 14 days. The levels of follicle-stimulating hormone, luteinizing hormone, estradiol, malondialdehyde, superoxide dismutases, apoptosis, and histopathological alterations were analyzed. Gas chromatography-mass spectrometry analysis was performed to identify the phytochemicals of the UPS. Results: It was observed that the UPS extract reduced malondialdehyde concentration and apoptosis in the DOR model as well as enhanced superoxide dismutases activity in the ovaries in a dose-dependent manner. Moreover, it exerted a modulatory effect on steroidal hormones such as follicle-stimulating hormone, luteinizing hormone, and estradiol. The histopathological analysis revealed the therapeutic potential of the UPS extract. The main chemical components of UPS were linoleic acid (59.25%), n-hexadecanoic acid (10.36%), and oleic acid (8.29%). Conclusion: The results indicated that the UPS extract has therapeutic potential in the DOR model. This potential is attributed to the reduction of oxidative stress, modulation of apoptosis, and regulation of steroidal hormones that may be associated with the observed beneficial effects of fatty acids on fertility improvement.

Effectiveness of Persian Golnar on Excessive Menstrual Bleeding in Women with Abnormal Uterine Bleeding, Compared to Tranexamic Acid: A Triple-Blind, Randomized Equivalence Trial.

Introduction: Abnormal uterine bleeding (AUB) is a major healthcare problem in females of reproductive age and impacts women's health and quality of life (QoL). This study aimed to test the equivalence of Persian Golnar (PG) and tranexamic acid (TA) for the treatment of excessive menstrual bleeding. Method: A triple-blind randomized equivalence trial with parallel design and block randomization technique was performed. A total of 80 patients with AUB were randomly allocated to receive either PG or TA for three consecutive menstrual cycles. Blood loss was measured by the Pictorial Blood Loss Assessment Chart (PBAC). Hematological evaluations were done before the intervention and after treatment. QoL and premenstrual dysphoric disorder (PMDD) as secondary outcomes were assessed using the menorrhagia questionnaire (MQ) and Premenstrual Symptoms Screening Tool (PSST). Statistical analysis was performed using an independent t-test, paired t-test, χ2 test, Mann-Whitney test, and Wilcoxon signed-rank test. Results: Seventy-six women completed the 12-week follow-up. Both PG and TA groups experienced a significant reduction in blood loss. Furthermore, the serum level of hemoglobin in the PG group enhanced significantly (P < 0.001). QoL and PMDD scores were significantly improved in both groups (P< 0.001). Conclusion: The findings of the current trial supposed that the Golnar product is as effective as tranexamic acid in controlling bleeding and enhancing the quality of life and premenstrual symptoms.

Major and minor criteria for gastric dystemperaments in Persian Medicine: Sari gastric dystemperament criteria-I (SGDC-I).

Background: Gastric disorders are one of the most common human ailments, which impose a huge economic burden on countries. In Persian Medicine (PM), it is possible to predict the susceptibility to gastric diseases with diagnosis of gastric Mizajes (temperaments) and dystemperaments. The semiology of gastric dystemperaments has been investigated in PM textbooks, although the value of each sign and symptom is not mentioned. Consequently, this research is designed to determine the major and minor criteria for classifying gastric dystemperaments on the basis of valid manuscripts and with the help of PM specialists in the present era. Methods: This was a consensus-based study consisting of four phases. In the first phase, reference PM textbooks were studied. Symptoms and signs of gastric dystemperaments were collected and listed in four groups. In the second phase, semi-structured interviews with a sample of PM experts were carried out. Phase three included a focused group discussion with experts. Eventually, findings were integrated from the three study phases in a two-day meeting in Sari City. Results: Selected criteria included eight major and eight minor criteria for hot-cold dystemperament, as well as six major and eight minor criteria for wet-dry gastric dystemperament. Conclusion: Modern lifestyles and the interfering factors are responsible for some changes in diagnostic signs and symptoms according to PM. This was the first step to coordinate PM diagnostic criteria for gastric dystemperaments. Further studies are recommended to reach a unique protocol in the field of PM diagnostics. The next step includes design and validation of national diagnostic tools.

Comparison between the Efficacy of Nigella sativa-Honey and Clotrimazole on Vulvovaginal Candidiasis: A Randomized Clinical Trial.

Materials and Methods: This triple-blind, randomized controlled trial was conducted on eighty-four 18 to 49-year-old nonpregnant women from August 2019 to February 2020. The subjects were randomly divided into two groups after confirming the diagnosis of VVC infection through fungal culture. Clinical signs and symptoms and lab tests were recorded at baseline and 6-10 days after treatment. The treatment time for each group was seven nights. Results: There were no significant differences in clinical and laboratory evaluations between the two groups at the beginning of the study (P > 0.05). After treatment, secretion, redness, itching, and fungal culture improved in the two groups (P < 0.001), while pruritus (p = 0.013) and secretion (p = 0.025) in the control group significantly improved. In this trial, no patients showed drug-specific side effects. Conclusion: The results of this study show that the N. sativa-honey significantly improves the symptoms of VVC; thus, the application of N. sativa-honey can be considered as a complementary therapy in the treatment of VVC. This trial is registered with IRCT20190711044176N1.

Effect of Garlic (Allium sativum) Supplementation on Premenstrual Disorders: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Premenstrual disorders involve physical, behavioral, and mood variations that affect women of childbearing age and interfere with family relationships, household responsibilities, professional duties, and social activities. OBJECTIVES: Considering the side effects of conventional medications, their use is not recommended except in severe cases of premenstrual disorders. Nowadays, there is a tendency to use traditional and complementary medicine that offers various treatments. The purpose of the current study was to investigate the impacts of garlic as a herbal medicine on the severity of premenstrual symptoms. METHODS: This study was a double-blind, randomized, controlled trial. After identification of participants with moderate-to-severe PMS through the premenstrual symptoms screening tools questionnaire (PSST), they were randomly assigned to placebo (n = 64) or garlic (n = 65) groups. Each participant received one tablet daily for three consecutive cycles and logged the severity of their symptoms in the PSST questionnaire during the intervention period. RESULTS: There was no significant difference between the two groups in the baseline level of premenstrual symptoms before the intervention. After treatment with garlic for three consecutive cycles, the total score of the severity of premenstrual symptoms significantly (P < 0.001) reduced from 34.09 ± 7.31 to 11.21 ± 7.17. In the placebo group, this score changed from 33.35 ± 7.96 to 24.28 ± 7.22. The difference between mean changes in the two groups was 13.78, with a 95% Confidence Interval (CI) of 11.23-16.33. No serious side effects were observed in either group. CONCLUSION: Our findings highlight the potential effect of garlic in reducing the severity of premenstrual symptoms; therefore, the use of garlic can be considered as an alternative therapy in the prevention and treatment of premenstrual disorders.

The Effect of Jazar Supplement on Quality of Life and Sexual Function in Postmenopausal Women: A Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Menopause is one of the most critical stages of a woman's life and is accompanied by symptoms including hot flashes, night sweats, mood swings, sexual dysfunction, mucus atrophy, and vaginal dryness. Women tend to use complementary and alternative medicine such as herbs rather than hormone replacement therapy to alleviate these symptoms. The purpose of this study is to examine the effects of Jazar supplement (herbal supplement comprising Vitex, fennel, and carrot seeds) on sexual function, quality of life, and vaginal atrophy in postmenopausal women. METHODS: This study was a randomized clinical trial conducted on ninety postmenopausal women. Participants were randomized to intervention/control groups using block randomization. The intervention group received four Jazar capsules (500 mg each) daily, while the control group received a placebo for eight weeks. Data were gathered using a socio-demographic questionnaire, the Female Sexual Function Index (FSFI), and the Menopause-Specific Quality of Life (MENQOL) before the intervention and at weeks 4, 8, and 10. Vaginal pH and vaginal maturation index (VMI) were measured before and at the end of the study. RESULTS: Eighty-four women completed the trial, and six women withdrew. There were no remarkable differences between the two groups in terms of quality of life, sexual function, VMI, and vaginal pH at baseline. At the end of the study, participants in the intervention group had a significantly lower score in terms of quality of life (P < 0.001) and vaginal pH (P=0.001), and a higher FSFI (P < 0.001) and VMI (P=0.030) score compared to the control group. CONCLUSION: Based on the findings of the present study on menopausal women, the Jazar supplement significantly improved quality of life and sexual function and prevented or delayed vaginal atrophy.

Efficacy of a vaginal tablet as a Persian medicine product on vulvovaginal candidiasis: a double-blind, randomised, placebo-controlled trial.

Context: In Persian medicine, topical ingredients such as Rosa damascena Mill. (Rosaceae), are usually recommended for the treatment of uterine diseases. Scientific evaluation of these historical documents can be valuable for finding new potential use in conventional medicine.Objective: This clinical trial was performed to determine whether the use of the 'ward' vaginal tablet, which contains Rosa damascena, Punica granatum L. (Punicaceae), Querqus infectoria Oliv. (Fagaceae), Myrtus communis L. (Myrtaceae) and Nardostachys jatamansi (D.Don) DC. (Caprifoliaceae) could alleviate the symptoms of vulvovaginal candidiasis.Materials and methods: A parallel double-blinded placebo-controlled study was done. Eighteen to fifty-year-old women with vulvovaginal candidiasis were divided into the 'ward' and placebo groups, 46 individuals in each group. The 'ward' group received the 'ward' vaginal tablet containing 200 mg of dried extract. Placebo group received a placebo (composed of corn starch and lactose). One tablet was applied through the vagina for 7 consecutive nights.Results: Two weeks after medication administration, the vaginal discharge sample of patients was re-cultured; 29 patients (63.045%) in the 'ward' group and 6 (13.04%) patients in the placebo group had negative culture (p < 0.001). All clinical symptoms including itching, irritation, and vaginal discharge were significantly reduced in the 'ward' group compared with the placebo group following the intervention and the follow up (p < 0.05).Discussion and conclusions: The findings suggest the 'ward' vaginal tablet could ameliorate vulvovaginal candidiasis. Future larger studies are recommended due to compare the therapeutic effect of the 'ward' vaginal tablet with common treatments.

Phytochemical profiling and ameliorative effects of Achillea cretica L. on rat model of endometriosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Achillea cretica (AC) is a medicinal plant emphasized for treatment of gynecological disorders and pathological symptoms similar to endometriosis in traditional Persian medicine. Since information about its chemical constituents is limited, the aim of this study is to investigate phenolic composition of AC extract as well as its effect on experimental model of endometriosis. MATERIALS AND METHODS: RP-HPLC-PDA-ESI-MS/MS analysis was used for the determination of polyphenolic compounds. Endometriosis was induced in rats by suturing of uterus segments to abdominal wall of same rat, after eight weeks when the model was induced, it was followed by 28 days of treatment with 100, 200, and 400 mg/kg/day of hydroethanolic extract of the plant. Blood samples and implanted tissues were collected in the final day, and area of foci, tumor necrosis factor-α, vascular endothelial growth factor, interleukin-6, and serum total thiol molecules were measured and compared with positive group (0.2 mg/kg/day letrozole) and control group (solvent of extract: normal saline). Implanted tissue sections of the sacrificed rats were also assessed histopathologically. RESULTS: Nine polyphenolic compounds were identified in AC extract including 7 flavonoids and 2 phenolic acids. Plant extract decreased area of foci and cytokine levels in serum and local tissue. Histopathological assessments confirmed the effectiveness of treatments by decreasing the thickness of epithelial layer and increasing the infiltration of leukocytes into this layer. Doses of 100 mg/kg and 400 mg/kg of extract showed better effects in comparison with the dose of 200 mg/kg in reduction of cytokine levels and size of implanted tissue. Extract and letrozole did not demonstrate significant effect on thiol level. CONCLUSION: AC aerial extract may be a favorable medicine for management of endometriosis by modulating inflammatory cytokines; however, further studies are needed for more conclusive and reliable decision about its efficacy and safety.

The Effects of Aromatherapy on Premenstrual Syndrome Symptoms: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

ObjectivesPremenstrual syndrome (PMS) is a common disturbance among women of childbearing age. Aromatherapy is a commonly used form of complementary and alternative medicine (CAM) to treat PMS. The purpose of this study is to quantify and summarize the effects of aromatherapy on premenstrual syndrome symptoms. Methods. PubMed, Scopus, and Cochrane Library databases were searched through relevant search terms until October 2020. The effect sizes were pooled as weighted mean difference (WMD) and 95% confidence interval (CI) using the random effect model. Egger tests and visual inspection of the funnel plot were performed to identify the existence of publication bias. The I-squared (I 2) test was applied to measure heterogeneity. Results. Eight studies (n = 8) were included in this analysis. The quantitative synthesis of evidence found that aromatherapy decreases PMS scores (WMD -13.83; 95% CI (-22.04, -5.63), I 2 = 94.5%), total psychological symptoms of PMS (WMD -3.51; 95% CI (-4.84, -2.18), I 2 = 82.6%), anxiety of PMS (WMD-1.78; 95% CI (-3.17, -0.38), I 2 = 94.2%), depression of PMS (WMD-2.0; 95% CI (-3.65, -0.34), I 2 = 93.7%), and fatigue of PMS (WMD - 1.44; 95% CI (-2.44, -0.44), I 2 = 89.7%) compared to the control group. Conclusion. Aromatherapy is an effective tool for the relief of PMS symptoms. Additional randomized controlled clinical trials with different durations and essential oils should be conducted to confirm our findings.

Use of mineral waters in the treatment of psoriasis: Perspectives of Persian and conventional medicine.

Psoriasis is a chronic inflammatory disease, which is accompanied by social and emotional complications leading to considerable disability. There is no definitive cure and treatment options carry complications. Balneotherapy has been used for years in psoriasis. Antibiotic, keratolytic, and anti-inflammatory effects of these waters have been proved. Persian medicine (PM) is a source of natural remedies for skin disease. The aim of study is to explain scientific evidences of Persian mineral waters as a treatment option for psoriasis. This is a narrative review, which investigates medical manuscripts of medieval Persia from 10th to 19th centuries AD noted as credible textbooks about mineral waters. Furthermore, balneotherapy evidences searched in databases including Pubmed, Scopus, and Cochrane until December 2017 to obtain clinical evidences related to psoriasis. In PM, mineral waters have keratolytic activity and can regulate superficial skin layers hyperproliferation, which is recommended for psoriasis treatment. In various studies, antiproliferative, keratolytic, antibiotic, anti-inflammatory, and antioxidant effects of these waters have been proved completely. There are scientific evidences, which demonstrate that mineral waters in Persia, can reduce clinical symptoms of psoriasis and improve quality of life in patients. Therefore, this method might be considered as treatment options for psoriasis.

Plant-derived medicines for treatment of endometriosis: A comprehensive review of molecular mechanisms.

Endometriosis is an estrogen-dependent disease with inflammatory lesions at extra-uterine sites, causing pelvic pain and fertility reduction. Conventional therapies primarily focus on reducing systemic levels of estrogens; however, they do not have desirable effectiveness and possess considerable side effects. Therefore, there is a growing interest in the use of herbal medicine for the treatment of endometriosis. In this paper, electronic databases including PubMed, Scopus, Cochrane library and Google Scholar were searched to obtain any studies evaluating any herbal products in the management of endometriosis. Data were collected from 1980 to 2018. Most of studies investigating the effect of herbal medicines in endometriosis were in vitro and animal and only three clinical trials were found; one on Pinus pinaster bark extract (Pycnogenol) and two on Chinese herbal formulas. The studies on phytochemicals had mostly focused on polyphenolic compounds (epigallocatechin-3-gallate, genistein) and sesquiterpenes (ß-caryophyllene, parthenolide). Various molecular mechanisms of action have been involved in beneficial effects of herbal medicines and phytochemicals including anti-inflammatory (via reduction of proinflammatory cytokines such as interleukin -1, interleukin -6, interleukin -8, transforming growth factor-beta, tumor necrosis factor-α, nuclear factor-kappa B, growth factors, monocyte chemoattractant protein-1), antioxidant (through downregulation of hydrogen peroxide, malondialdehyde, reactive oxygen species and upregulation of superoxide dismutase), anti-proliferative and apoptotic (via enhancing Bcl-2-associated X protein/ B-cell lymphoma-2 and caspase3, 8 and 9 activity), anti-angiogenic (by downregulation of vascular endothelial growth factor receptors/ vascular endothelial growth factor), anti-invasive (via decreasing expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and matrix metalloproteinases), immunomodulatory, and estrogen modulating activities. So, medicinal plants seem to be a valuable source for identifying new drugs for treatment of endometriosis; however, since most of studies are preclinical, further clinical trials are required to achieve more conclusive results.

An Evidence-Based Review of Medicinal Plants Used for the Treatment of Vaginitis by Avicenna in "the Canon of Medicine".

Vaginitis is one of the most common gynecological problems in reproductive age. Because of the limitations of the conventional drugs, identification of new pharmacological interventions for this disease seems to be necessary. The purpose of this article is to review the medicinal herbs mentioned for the treatment of vaginitis by the great Iranian scientist, Avicenna, in his book "the Canon of Medicine " to scientifically demonstrate their effects and their potential to be used as complementary therapies. The medicinal plants listed for vaginitis treatment in "the Canon of Medicine " were extracted. The scientific name and English common name of the given medicinal plants were searched in databases including PubMed, Scopus, and Cochrane Library until December 2017 to obtain any in vitro, animal, and clinical evidence related to vaginitis. Various pharmacological activities, including anti-inflammatory, wound healing, antimicrobial, antifungal, analgesic, and anti-prostaglandin E2, have been demonstrated for medicinal plants emphasized by Avicenna for vaginitis. Randomized controlled trials (RCTs) on Myrtus reported an improvement in the treatment of bacterial vaginosis. Four RCTs on pomegranate indicated a reduction in inflammatory factors in the patients. Medicinal herbs offered in Herbal Medicine are valuable sources for the treatment of various diseases. Effects and pharmacodynamics having been proved by conventional medicine confirm the effectiveness of these herbs. Therefore, these plants can be used in the treatment of vaginitis thanks to further clinical studies.

The Challenges of Clinical Researches in Iranian Traditional Medicine (ITM).

BACKGROUND: Traditional medicine is one of the medical schools, which has been considered in recent years. Achieving reliable and valid research in ITM is very important to introduce this line of medicine into the healthcare organizations. The aim of this study was to investigate clinical research issues in ITM. METHODS: This study is a qualitative research. We formed an expert panel and, after identifying the content, the study findings were divided into two main categories. RESULTS: Challenges of clinical research studies are divided into two major categories in ITM, the problems of clinical trial processes and the difficulties in publishing research results. Lack of standard data collection instruments and questionnaires, limited sample size, lack of study models designed for distemperament treatment, unawareness, and non-compliance of ethics committees in facilities approved by WHO for clinical research of TM, and even rigidity beyond conventional medicine studies are some of the previously mentioned issues. Some difficulties in the publication of research results include lack of specialized journals especially at high academic levels, lack of familiarity with editorial board and difficulty in publishing the results of studies that are designed with combined products. A few proposals for these problems include: Conducting codification questionnaire workshops (approved by a thesis assistant with a subject of research tools)Introducing appropriate methods of multi-intervention research in ITMCreating the database of similarly performed research available for researchersDesigning multicenter researchCollaborations between academic centersLinking two or more thesis assistants or research projects in the form of a joint proposal with larger sample sizesEstablishing joint meeting between researchers, the heads of TM research centers and ethics committeesDedicated TM journal. CONCLUSION: Considering a history of several thousand years, the Iranian traditional medicine is a great venue for students. To establish and distribute the information from this research field, collaboration between researchers and policy makers are essential to minimize challenges.

Menorrhagia Management in Iranian Traditional Medicine.

Menorrhagia is a common problem. Medical management for menorrhagia includes hormonal and nonhormonal treatments. These treatments have different side effects, which reduce quality of life. Complementary and traditional medicines have been used to handle menorrhagia for centuries in many cultures. There is a lot of information and data in Iranian traditional documents or books about medicinal herbs that are used by Iranian traditional medicine scientists for the treatment of menorrhagia. The aim of this study was to review the approaches to menorrhagia in Iranian traditional medicine texts. In this study, some main Iranian traditional medicine manuscripts including Canon of Medicine and Al-Havi of Rhazes were studied to extract important information about menorrhagia management. Iranian traditional medicine physicians have relied on an organized system of etiological theories and treatments for menorrhagia. Their methods for menorrhagia management may be able to convince the desire of many women to preserve their uterus and avoid hormonal therapy.